The objectives of this project are to characterize the molecular control of myeloid leukemia cells by first establishing the nature of the specific glycoproteins (colony-stimulating factors, CSFs) controlling cell division and differentiation of normal granulocytes and macrophages, then determining the actions of the CSFs on leukemia cells. We have established that four glycoproteins interact to control normal mouse granulocytes and macrophages: GM-CSF, M-CSF, G-CSF, and Multi-CSF (IL-3). All four have been purified to homogeneity in small amounts. Sequence data from GM-CSF have allowed us to isolate a cDNA clone for GM-CSF and to establish that the polypeptide portion of GM-CSF contains 118 amino acids (Mr = 13,500). Although GM-CSF and Multi-CSF function in a similar manner, there is no primary or secondary homology between the two polypeptides nor is there sequence homology with known oncogenes. We have established that G-CSF can suppress myeloid leukemic cells by enforcing terminal differentiation. Using 125I-labeled G-CSF, we have shown that receptor numbers on leukemia cells are similar to those on normal GM precursor cells. Differentiation-unresponsive leukemia cells have been shown to lack membrane receptors for G-CSF. These studies will be extended using radiolabeled GM-CSF, and the genetic elements controlling GM-CSF will be sequenced and analyzed. We will also attempt to obtain amino acid sequence data from purified G-CSF and to obtain a cloned cDNA for G-CSF, a first step towards the mass production of G-CSF. (M)